Incidence and Risk Factors of Parenteral Nutrition-Associated Cholestasis in Omani Neonates; Single centre experience

Objectives: Parenteral nutrition-associated cholestasis (PNAC) is one of the most challenging complications of prolonged parenteral nutrition (PN) in neonates. There is a lack of research investigating its incidence in newborn infants in Oman and the Arab region. Therefore, this study aimed to assess the incidence of PNAC and its risk factors in Omani neonates. Methods: This retrospective study took place between January and April 2014. All neonates who received PN for ≥14 days during a four-year period (June 2009 to May 2013) at the neonatal intensive care unit (NICU) in Sultan Qaboos University Hospital, Muscat, Oman, were enrolled. Results: A total of 1,857 neonates were admitted to the NICU over the study period and 135 neonates (7.3%) received PN for ≥14 days. Determining the incidence of PNAC was only possible in 97 neonates; of these, 38 (39%) had PNAC. The main risk factors associated with PNAC were duration of PN, duration of enteral starvation, gastrointestinal surgeries, blood transfusions and sepsis. Neonates with PNAC had a slightly higher incidence of necrotising enterocolitis in comparison to those without PNAC. Conclusion: This study found a PNAC incidence of 39% in Omani neonates. There were several significant risk factors for PNAC in Omani neonates; however, after logistic regression analysis, only total PN duration remained statistically significant. Preventive strategies should be implemented in NICUs so as to avoid future chronic liver disease in this population

LHFPL5 mutation: A rare cause of non-syndromic autosomal recessive hearing loss

Hearing loss is a debilitating disorder that impairs language acquisition, resulting in disability in children and potential isolation in adulthood. Its onset can have a genetic basis, though environmental factors, which are often preventable, can also cause the condition. The genetic forms are highly heterogeneous, and early detection is necessary to arrange appropriate patient support. Here we report the molecular basis of hereditary hearing loss in a consanguineous family with multiple affected members from Oman. Combining homozygosity mapping with whole exome sequencing identified a novel homozygous nucleotide substitution c.575T > C in the lipoma HMGIC fusion partner-like 5 gene (LHFPL5), that converted the 192nd amino acid residue in the protein from a leucine to a proline, p.(Leu192Pro). Sanger sequencing confirmed segregation with the disease phenotype as expected for a recessive condition and the variant was absent in 123,490 subjects from various disease-specific and population genetic studies as well as 150 unrelated individuals and 35 deaf patients of Omani ethnicity. This study, which describes a novel LHFPL5 mutation in a family of Omani origin with hereditary hearing loss, supports previous clinical descriptions of the condition and contributes to the genetic spectrum of mutations in this form of deafness

THUMPD1 bi-allelic variants cause loss of tRNA acetylation and a syndromic neurodevelopmental disorder.

Covalent tRNA modifications play multi-faceted roles in tRNA stability, folding, and recognition, as well as the rate and fidelity of translation, and other cellular processes such as growth, development, and stress responses. Mutations in genes that are known to regulate tRNA modifications lead to a wide array of phenotypes and diseases including numerous cognitive and neurodevelopmental disorders, highlighting the critical role of tRNA modification in human disease. One such gene, THUMPD1, is involved in regulating tRNA N4-acetylcytidine modification (ac4C), and recently was proposed as a candidate gene for autosomal-recessive intellectual disability. Here, we present 13 individuals from 8 families who harbor rare loss-of-function variants in THUMPD1. Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism, and ophthalmological abnormalities. We demonstrate that the bi-allelic variants identified cause loss of function of THUMPD1 and that this defect results in a loss of ac4C modification in small RNAs, and of individually purified tRNA-Ser-CGA. We further corroborate this effect by showing a loss of tRNA acetylation in two CRISPR-Cas9-generated THUMPD1 KO cell lines. In addition, we also show the resultant amino acid substitution that occurs in a missense THUMPD1 allele identified in an individual with compound heterozygous variants results in a marked decrease in THUMPD1 stability and RNA-binding capacity. Taken together, these results suggest that the lack of tRNA acetylation due to THUMPD1 loss of function results in a syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss, and facial dysmorphism

THUMPD1 bi-allelic variants cause loss of tRNA acetylation and a syndromic neurodevelopmental disorder

Covalent tRNA modifications play multi-faceted roles in tRNA stability, folding, and recognition, as well as the rate and fidelity of translation, and other cellular processes such as growth, development, and stress responses. Mutations in genes that are known to regulate tRNA modifications lead to a wide array of phenotypes and diseases including numerous cognitive and neurodevelopmental disorders, highlighting the critical role of tRNA modification in human disease. One such gene, THUMPD1, is involved in regulating tRNA N4-acetylcytidine modification (ac4C), and recently was proposed as a candidate gene for autosomal-recessive intellectual disability. Here, we present 13 individuals from 8 families who harbor rare loss-of-function variants in THUMPD1. Common phenotypic findings included global developmental delay, speech delay, moderate to severe intellectual deficiency, behavioral abnormalities such as angry outbursts, facial dysmorphism, and ophthalmological abnormalities. We demonstrate that the bi-allelic variants identified cause loss of function of THUMPD1 and that this defect results in a loss of ac4C modification in small RNAs, and of individually purified tRNA-Ser-CGA. We further corroborate this effect by showing a loss of tRNA acetylation in two CRISPR-Cas9-generated THUMPD1 KO cell lines. In addition, we also show the resultant amino acid substitution that occurs in a missense THUMPD1 allele identified in an individual with compound heterozygous variants results in a marked decrease in THUMPD1 stability and RNA-binding capacity. Taken together, these results suggest that the lack of tRNA acetylation due to THUMPD1 loss of function results in a syndromic form of intellectual disability associated with developmental delay, behavioral abnormalities, hearing loss, and facial dysmorphism.The article is available via Open Access. Click on the 'Additional link' above to access the full-text.Published version, accepted version (6 month embargo), submitted versio

Not Available

Not AvailableThe extinction risk of sharks, rays and chimaeras is higher than that for most other vertebrates due to low intrinsic population growth rates of many species and the fishing intensity they face. The Arabian Sea and adjacent waters border some of the most important chondrichthyan fishing and trading nations globally, yet there has been no previous attempt to assess the conservation status of species occurring here. Using IUCN Red List of Threatened Species Categories and Criteria and their guidelines for application at the regional level, we present the first assessment of extinction risk for 153 species of sharks, rays and chimaeras. Results indicate that this region, home to 15% of described chondrichthyans including 30 endemic species, has some of the most threatened chondrichthyan populations in the world. Seventy‐eight species (50.9%) were assessed as threatened (Critically Endangered, Endangered or Vulnerable), and 27 species (17.6%) as Near Threatened. Twenty‐nine species (19%) were Data Deficient with insufficient information to assess their status. Chondrichthyan populations have significantly declined due to largely uncontrolled and unregulated fisheries combined with habitat degradation. Further, there is limited political will and national and regional capacities to assess, manage, conserve or rebuild stocks. Outside the few deepsea locations that are lightly exploited, the prognosis for the recovery of most species is poor in the near‐absence of management. Concerted national and regional management measures are urgently needed to ensure extinctions are avoided, the sustainability of more productive species is secured, and to avoid the continued thinning of the regional food security portfolio.Not Availabl

Not Available

Not AvailableThe extinction risk of sharks, rays and chimaeras is higher than that for most other vertebrates due to low intrinsic population growth rates of many species and the fishing intensity they face. The Arabian Sea and adjacent waters border some of the most important chondrichthyan fishing and trading nations globally, yet there has been no previous attempt to assess the conservation status of species occurring here. Using IUCN Red List of Threatened Species Categories and Criteria and their guidelines for application at the regional level, we present the first assessment of extinction risk for 153 species of sharks, rays and chimaeras. Results indicate that this region, home to 15% of described chondrichthyans including 30 endemic species, has some of the most threatened chondrichthyan populations in the world. Seventy‐eight species (50.9%) were assessed as threatened (Critically Endangered, Endangered or Vulnerable), and 27 species (17.6%) as Near Threatened. Twenty‐nine species (19%) were Data Deficient with insufficient information to assess their status. Chondrichthyan populations have significantly declined due to largely uncontrolled and unregulated fisheries combined with habitat degradation. Further, there is limited political will and national and regional capacities to assess, manage, conserve or rebuild stocks. Outside the few deepsea locations that are lightly exploited, the prognosis for the recovery of most species is poor in the near‐absence of management. Concerted national and regional management measures are urgently needed to ensure extinctions are avoided, the sustainability of more productive species is secured, and to avoid the continued thinning of the regional food security portfolio.Not Availabl